Elevated liver transaminases among patients with psychiatric disorders.

Hepatocyte injury is assessed by serum aspartate transaminase and alanine transaminase estimation. In psychiatric populations, antipsychotic drugs (AD) are culprit in hepatic dysfunction. To assess transaminitis among psychiatric patients treated by AD. This cross-sectional study was conducted in Zagazig University Hospitals in Egypt, from December 2022 to February 2023. A total of 135 adult patients aged ≥ 18 years, were diagnosed with psychiatric disorders after exclusion of patients receiving any hepatotoxic drugs, viral hepatitis, having chronic liver or kidney diseases, diabetes mellitus, mental retardation, and pregnant females. Among the 135 patients, 104 (77.0%) were males. Their age was 32 ±â€…9, The most popular used class of AD was atypical AD 84 (62.2%). The overall incidence of transaminitis among patients receiving AD was 23/135 (17.04%) of patients; 13 (56.5%) were on atypical AD compared to 10 (43.5%) patients receiving combined AD, without any statistically significant difference. The use of AD in patients with psychiatric disorders is potentially safe with minimal transaminitis (

Electroconvulsive therapy improves hematological inflammatory markers in bipolar disorder.

BACKGROUND: Immune dysfunction and inflammation participate in the pathophysiology of bipolar disorder (BD). Abnormal levels of inflammatory markers, namely, red cell distribution width (RDW) and platelet distribution width (PDW), were detected in BD. Electroconvulsive therapy (ECT) for various mental disorders including BD was linked to changes in these inflammatory mediators. Hence, we aimed to assess the impact of ECT on PDW and RDW in patients with BD. METHODS: Seventy-two patients aged ≥ 16 were enrolled in the current prospective cohort study over 6 months, diagnosed as BD based on DSM-IV and indicated for ECT and complete blood count (CBC) drawn pre-ECT and after four ECT sessions. RESULTS: By the end of the ECT sessions, we noticed a significant elevation in PDW with lowering in RDW levels. However, no significant differences were detected before and after ECT regarding platelet (PLTs) count, mean platelet volume (MPV), and Plateletcrit (PCT). CONCLUSION: ECT seems to improve the CBC-derived inflammatory markers (RDW and PDW) subsequently, improving the underlying inflammatory process in BD without disturbing PLT homeostasis which support its anti-inflammatory role in BD.

Real-Life Experience in the Efficacy and Safety of COVID-19 Vaccination in Patients with Advanced Cirrhosis.

COVID-19 infections accelerate liver decompensation and serious liver-related co-morbidities. The aim is to evaluate the safety and impact of COVID vaccines on hepatic disease progression in patients with advanced liver disease and to identify parameters that predict the occurrence of complications. The study involved 70 patients with advanced liver disease who were vaccinated with different COVID vaccines from January 2021 to April 2022. They were evaluated clinically. The laboratory investigation included a complete blood count, liver and kidney function tests, calculation of CTP and MELD scores, plasma levels of ammonia, abdominal ultrasound, and upper GI endoscopy. Twenty patients had experienced complications 64 ± 12 days from the last dose of a vaccination. Twenty patients (28.6%) developed hepatic decompensation and hypothyroidism (n = 11, 15.7%), and five (7.14%) patients developed splanchnic thrombosis. There were no COVID-19 reinfections except for two patients who received Sinopharm and developed vaccine-associated enhanced disease (2.9%). Complications after COVID vaccinations were correlated with ALT (r = 0.279, p = 0.019), serum sodium (r = -0.30, p = 0.005), creatinine (r = 0.303, p = 0.011), liver volume (LV) (r = -0.640, p = 0.000), and MELD score (r = 0.439, p = 0.000). Multivariate logistic regression revealed that LV is the only independent predictor (p = 0.001). LV ≤ 682.3 has a sensitivity of 95.24% and a specificity of 85.71% in predicting complications with an AUC of 0.935, p < 0.001. In conclusion, the hepatic reserve and prognosis in liver cirrhosis should be evaluated prior to COVID vaccinations using the MELD score and liver volume as promising risk stratification criteria. In summary, the research proposes a novel triaging strategy that involves utilizing the MELD score and liver volume as risk stratification parameters of the hepatic reserve and prognosis of advanced liver cirrhosis prior to COVID immunization to determine who should not receive a COVID vaccination.

TOX Outperforms FOXP3, CD4 and GATA3 in Histopathological Diagnosis of Early Mycosis Fungoides.

OBJECTIVE: Mycosis fungoides (MF) is the most common type of cutaneous lymphoma. The early stage of MF is a difficult diagnostic case, as it is often confused with many benign inflammatory dermatoses (BID). The study aimed to evaluate the diagnostic utility of TOX, FOXP3, CDD4 and GATA3 in differentiating early stages of MF from histologically overlapping BID lesions. MATERIAL AND METHOD: A retrospective cross-sectional study was performed, in which immunohistochemistry (IHC) was used to evaluate the expression of TOX, FOXP3, CD4 and GATA3 in formalin-fixed paraffin-embedded (FFPE) sections of skin lesions from 30 cases with BID and 30 patients with early-stage MF. RESULTS: The association between TOX expression and early-stage MF was statistically significant (P < 0.001). TOX had the highest sensitivity of 96.77% and accuracy of 85.71% in diagnosis of MF; followed by CD4 with sensitivity of 85.71% and accuracy of 78.95%; and then, GATA3 with sensitivity of 76.7% and finally FOXP3 with sensitivity of 70.0%. CONCLUSION: TOX is suggested to be of higher diagnostic value in the early stages of MF than the conventionally used CD4 and other markers examined.

Clinical utility of haematological inflammatory biomarkers in predicting 30-day mortality in hospitalised adult patients with COVID-19.

Coronavirus disease 2019 (COVID-19) is a multisystem disease affecting respiratory, cardiovascular, gastrointestinal, neurological, immunological and haematological systems. The most important indices that have been studied are platelet (PLT) indices in addition to the PLT count and red blood cell distribution width (RDW). This retrospective study included 95 patients with COVID-19 and was conducted at the Hospital Isolation, Scientific and Medical Research Centre and Clinical Pathology Department at Zagazig University Hospitals, Egypt over 6 months from March to August 2021. All patients on admission had a full blood count, which included white blood cell (WBC) count, haemoglobin, RDW, PLT count and its indices in addition to PLT-to-WBC ratio (PWR) and PLT-to-lymphocyte ratio (PLR), which were calculated for all the study patients. There were significant linear correlations for higher levels of the PLR, PWR and RDW and mortality rate (p = 0.03, p < 0.001 and p < 0.001 respectively). Moreover, on multivariable analysis the RDW, PLT count and PWR levels were independent prognostic predictors for mortality with a hazard ratio [HR] of 1.25 (95% confidence interval [CI] 1.09-1.44, p = 0.002), 1.00 (95% CI 0.99-1.00, p = 0.03) and 2.3 (95% CI 1.21-4.48, p = 0.01) respectively. The RDW and PLT indices are accessible predictors that can be valuable prognostic factors for survival assessment and risk stratification of COVID-19.

Expression of epithelial-mesenchymal transition biomarkers: Discoidin domain receptor 2, Snail-1, and Ovol-2 as predictors of clinical outcome in patients with epithelial ovarian carcinoma.

Context: Discoidin domain receptor 2 (DDR-2), which belongs to the receptor tyrosine kinase family, Snail-1, which is a member of zinc-finger transcription factor family, and Ovol-2, which is a member of Ovol family, are incriminated in epithelial-mesenchymal transition (EMT) during cancer progression. Aim: In the current study, we aim to clarify the extent to which EMT biomarkers, DDR-2, Snail-1, and Ovol-2 expression, are involved in the progression of EOC aiming at identification of novel markers for predicting the prognosis of EOC patients. Settings and Design: This was a prospective cohort that was performed in the Faculty of Medicine, Zagazig University. Materials and Methods: We evaluated DDR-2, Snail-1, and Ovol-2 expression in 60 patients of EOC using immunohistochemistry. We followed our patients for about 36 months and analyzed the relationship between markers expression and the prognosis of patients. Statistical Analysis Used: SPSS program (Statistical Package for the Social Sciences). Results: High expression of both DDR-2 and Snail-1 was related to higher grade (P = 0.006) and advanced FIGO stage of the tumor (P < 0.001). Ovol-2 high expression was associated with lower grade of the tumor (P = 0.002) and early stage of the tumor (P < 0.001). High Ovol-2 and low DDR2 and Snail-1 expression were strongly correlated with better response to therapy (P = 0.003 and 0.005, respectively) and increased 3-year survival rates (P < 0.001). Conclusion: DDR-2 and Snail-1 are markers of poor prognosis in EOC while Ovol-2 is a marker of good prognosis.

Prognostic values of myeloid differentiation factor 88 (MYD88) and transducin (ß)-like receptor 1 (TBLR1) expression in tissues of diffuse large B-cell non-Hodgkin lymphoma patients - an immunohistochemical study.

Introduction: Diffuse large B-cell non- Hodgkin lymphoma (DLBCL) is the largest common category of adult lymphoma. Recurrence and treatment resistance occurs in one-third of cases, triggering them to the progressive stage of DLBCL after treatment. Detection of novel predictive and prognostic biomarkers leads to improvement of its treatment and prognosis. Aim of the study: To assess the prognostic roles of protein expression of myeloid differentiation factor 88 (MYD88) and transducin (ß)-like receptor 1 (TBLR1) in tissues of DLBCL patients. Material and methods: In the current study we included tissues from 100 cases of DLBCL. For immunohistochemistry, tissues were stained with MYD88 and TBLR1. We followed patients for about 3 years, and then we correlated their expression with clinicopathological and prognostic parameters. Results: Higher MYD88 and TBLR1 expressions were associated with presence of B symptoms, fever, night sweat, advanced stage, bone marrow involvement and bulky nodal size, presence of extra-nodal extension, unfavourable relapse-free survival, and unfavourable overall survival rates (p < 0.001). Conclusions: overexpression of MYD88 and TBLR1 expression was present in DLBCL patients and was associated with unfavourable clinicopathological and prognostic parameters.

Prognostic significance of lymphocyte-to-monocyte ratio in patients with classical Hodgkin lymphoma before and after receiving first-line chemotherapy.

Introduction: Despite the presence of a prognostic risk stratification sco-ring system for Hodgkin lymphoma (HL), the lymphocyte-to-monocyte ratio (LMR) is a simple and low-cost test that has been investigated as a prognostic marker to evaluate the clinical course and survival outcomes. Material and methods: We prospectively enrolled 92 patients with classical HL (CHL), who were diagnosed and treated in the period from April 2017 to April 2020. Lymphocyte monocyte ratio cut-off values were estimated using receiver operating characteristic curves. Results: We found that patients with LMR < 1.4 at the time of diagnosis had poorer progression-free survival (PFS) and overall survival (OS) than those with LMR > 1.4. Patients with increased LMR values after the first 2 cycles of chemotherapy had better PFS and OS; meanwhile, patients who had low LMR after the end of chemotherapy had poorer PFS and OS in comparison to patients who gained higher value after the completion of all cycles of chemotherapy. Conclusions: A rise of LMR value indicated better outcome and better survival rate, so it can be an independent prognostic factor for survival and to predict outcome in patients with CHL.

A comparison between different management surgical approaches in the treatment of splenic flexure colon cancer

Background: There are many surgical approaches which described extent of resection of the colon for adequate surgicalmanagement of splenic flexure cancer, but up till now there is no established surgical procedure, this is because the presence of double lymphatic drainage of themesenteric vessels. Segmental resection of the colon for the management of splenic flexure cancer was a recently accepted surgical procedure. Objective: In the present study, we aimed to compare three surgical management techniques to clarify the best management approach of Egyptian patients with splenic flexure cancer regarding operative, clinical, and oncological outcomes: segmental resection, and extended left or right hemicolectomy,. Materials and Methods In the present study, we included 90 patients with splenic flexure cancer. Cases were divided into 3 groups. Each group included 30 patients in order to compare three surgical techniques: segmental resection, extended left hemicolectomy, and extended right hemicolectomy. Results: We have found no statistically significant differences between the three included groups regarding operative findings, postoperative complications, local recurrence, distant recurrence, disease progression, recurrence-free survival rate, progression-free survival rate, and overall survival rate. The operative time was longer, and the number of lymph nodes was higher in the extended right hemicolectomy group (p<0.001). Conclusion: We have shown that segmental resection of the splenic flexure is surgically and clinically suitable for the adequate management of operable cases of carcinoma of the splenic flexure. (AU)

The Diagnostic and Prognostic Roles of Combined Expression of Novel Biomarkers in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma: An Immunohistochemical Study.

BACKGROUND & OBJECTIVE: Diagnosis and discrimination of lung adenocarcinoma (LUAD) from lung squamous cell carcinoma (LUSC) is critical to select the appropriate treatment regimen as recently targeted therapies require accurate subtyping of nonsmall-cell lung carcinoma (NSCLCs). There are currently several biomarkers that could be used for differentiation between LUAD and LUSC, but they have less sensitivity, specificity, and clinical applicability. The aim of this study was to assess the diagnostic and prognostic values of CLCA2, SPATS2, ST6GALNAC1, and Adipophilin tissue expression in the tissues retrieved from LUAD and LUSC patients using immunohistochemistry. METHODS: The current study was performed on the samples retrieved from sixty primary lung masses that were diagnosed as LUAD and LUSC. Immunohistochemistry was performed by using a panel of CLCA2, SPATS2, and ST6GALNAC1. We assessed the diagnostic roles of the studied markers in the discrimination between LUAD and LUSC and their prognostic values. RESULTS: SPATS2 and CLCA2 were expressed higher in LUSC than LUAD. ST6GALNAC1 and Adipophilin showed higher expression in LUAD than LUSC (P <0.001). The sensitivity and specificity of CLCA2, SPATS2, ST6GALNAC1 and Adipophilin in adequate subtyping and reaching the accurate diagnosis was 100%. We found only significant difference in survival rate between the patients with negative and positive CLCA2 expression (P=0.038 and P=0.019, respectively). CONCLUSION: The combination of biomarkers of CLCA2, SPATS2, ST6GALNAC1, and Adipophilin may lead to an appropriate subtyping of lung cancer and reaching accurate diagnosis with the highest sensitivity and specificity.

Initial absolute monocyte count as an immune biomarker for clinical response in acute myeloid leukemia with monocytic differentiation.

BACKGROUND: Absolute monocyte count (AMC) correlates with survival outcomes in various hematologic malignancies. However, its role in myeloid malignancies including AML needs to be highlighted. So, this prospective cohort study aimed to assess the effect of AMC on the treatment outcome and survival in a 56 adult de novo AML patients with monocytic differentiation, admitted to the Clinical Hematology Unit, Internal Medicine Department, in a tertiary referral hospital in Egypt, from July 2016 to June 2019. RESULTS: The initial AMC was measured either by manual differential or the hematology automatic analyzer Sysmex XN-2000 and patients were classified by using receiver operating characteristic curve into two groups monocytopenic (≤ 4 × 109/L) and non-monocytopenic (> 4 × 109/L) group; including 24 (42.9%) and 32 (57.1%) patients, respectively. After a median follow up period of 7.7 (range 0.5-33.2) months, the monocytopenic group was associated with a significantly higher CR rate (P = 0.019), with a lower death as well as relapse and early relapse rates (P = 0.011, 0.033, and 0.002, respectively). Moreover, low initial AMC along with intensive induction were independently associated with complete response to induction chemotherapy with HR, 5.04 [1.37-18.58], P = 0.015, and 5.67 [1.48-21.71], P = 0.011, respectively by using the multivariate logistic regression model. Regarding survival, the monocytopenic group was associated with a better 3-year disease-free survival rate (P = 0.011) in univariate Cox regression only but did not reach significance in the multivariate model and did not affect the overall survival as well. CONCLUSION: Initial AMC was found to be an independent prognostic immune biomarker for treatment response in AML patients with monocytic differentiation. However, it did not appear as an independent predictor of survival in a multivariate analysis.

Clinicopathological characterization and prognostic implication of FOXP3 and CK19 expression in papillary thyroid carcinoma and concomitant Hashimoto's thyroiditis.

Papillary thyroid carcinoma (PTC) is considered the most prevalent thyroid malignancy. The association between Hashimoto's thyroiditis (HT) and PTC is still unclear. We aimed to examine the clinicopathological impact of immunohistochemical staining of FOXP3 and Cytokeratin 19 in PTC and concomitant HT and their correlation with patients' outcome and survival. Eighty thyroid biopsies obtained from patients with PTC were immunostained by FOXP3 and CK19.The patients were treated by radioactive iodine (I131) and followed up. FOXP3 and CK19 expression were detected in 45% and 80% studied cases of PTC respectively. 16.7% of PTC with associated HT showed FOXP3+ lymphocytes in lymphocytic infiltrate of HT, while most of PTC associated HT express cytoplasmic CK19 positive Hurtle cells. FOXP3 was more expressed in PTC female patients more than 45 years with higher stage, lymph node, and distant metastasis, extracapsular extension, number of I131doses, and cumulative radioiodine doses with a highly statistically significant difference (p < 0.001). The relation was significant between CK19 immunostaining as regard 10-year Overall Survival and death (p value = 0.027 and 0.036, respectively). HT represents a step in the process of autoimmune inflammatory disease ending by the evolution of PTC with better prognosis, therefore appropriate follow up of these cases is needed. FOXP3 tends to be more expressed in PTC cases with worse prognostic variables and is predictable to become a recent prognostic and targeted therapy for PTC. There was a significant relation between CK19 immunostaining and 10 year overall survival.

Pyrazolyl-pyrimidones inhibit the function of human solute carrier protein SLC11A2 (hDMT1) by metal chelation.

Solute carrier proteins (SLCs) control fluxes of ions and molecules across biological membranes and represent an emerging class of drug targets. SLC11A2 (hDMT1) mediates intestinal iron uptake and its inhibition might be used to treat iron overload diseases such as hereditary hemochromatosis. Here we report a micromolar (IC50 = 1.1 µM) pyrazolyl-pyrimidone inhibitor of radiolabeled iron uptake in hDMT1 overexpressing HEK293 cells acting by a non-competitive mechanism, which however does not affect the electrophysiological properties of the transporter. Isothermal titration calorimetry, competition with calcein, induced precipitation of radioactive iron and cross inhibition of the unrelated iron transporter SLC39A8 (hZIP8) indicate that inhibition is mediated by metal chelation. Mapping the chemical space of thousands of pyrazolo-pyrimidones and similar 2,2'-diazabiaryls in ChEMBL suggests that their reported activities might partly reflect metal chelation. Such metal chelating groups are not listed in pan-assay interference compounds (PAINS) but should be checked when addressing SLCs.

Metallo-Organozymes with Specific Proteolytic Activity.

Metallopeptides that show efficiency and selectivity in peptide bond cleavage in water at room temperature and neutral conditions are presented. These small and versatile organozymes take advantage of metal-coordinating building blocks that are strategically positioned centrally in a peptide backbone or in a peptide macrocycle. This approach provided peptide-metal complexes with scaffolds capable of utilizing the peptide functionality for productive binding of fluorogenic FRET peptide substrates, subsequently leading to highly selective peptide bond cleavage. The ligand chemistry has been optimized to provide an easy access to new metallo-peptides with the ability to cleave previously inaccessible peptide bonds. Evolutionary principles of stepwise selection and variation offered by combinatorial methods were used and were guided by molecular modeling to develop catalytic metallo-peptides that mimic metalloproteases.

SPOP, ZEB-1 and E-cadherin expression in clear cell renal cell carcinoma (cc-RCC): Clinicopathological and prognostic significance.

BACKGROUND: Clear cell renal cell carcinoma (cc-RCC), is a serious cancer regarding; its fatality, liability for metastases and chemoresistance, so identification of recent therapeutic targets to improve the patients prognosis is needed. SPOP is a BTB/POZ domain containing speckle-type POZ protein, has been identified as an E3 ubiquitin ligase component. ZEB1 is an essential epithelial mesenchymal transition (EMT) activator; E-cadherin is a cell adhesion protein that had been detected in normal epithelial cells membrane. AIM: Was to assess the tissue protein markers SPOP, ZEB1 & E-cadherin expressions in benign areas of neoplastic kidney specimens and in cc-RCC patients, then correlating their expression levels with patients clinicopathological and prognostic data. METHODS: We evaluated SPOP, ZEB-1 & E-cadherin expression using immunohistochemistry in samples from 50 cc-RCC and 20 benign areas of neoplastic kidney specimens, then we followed our patients for 5 years and finally we have analyzed correlations between the levels of markers expressions with patients clinicopathological and prognostic criteria in cc-RCC. RESULTS: Positive expression of SPOP & ZEB1 in addition to negative E- cadherin expression was detected in cc-RCC more than benign areas of neoplastic kidney specimens (p = 0.004 and p < 0.001 respectively). In cc-RCC Positive expression of SPOP, ZEB1 and negative E- cadherin expression was associated with higher grade (p = 0.006, 0.007 & <0.001 respectively), advanced AJCC stage (p = 0.013, 0.023 & <0.001 respectively), presence of L.N metastases (p = 0.002 = 0.010 and <0.001 respectively), distant metastases (p = 0.001, 0.003 & 0.035 respectively), poor PFS and OS rates (p < 0.001 and p = 0.013 respectively). CONCLUSION: Positive expression of SPOP& ZEB1 in addition to negative E- cadherin are associated with poor prognosis in cc-RCC patients.

Rational Tuning of Fluorobenzene Probes for Cysteine-Selective Protein Modification.

Fluorobenzene probes for protein profiling through selective cysteine labeling have been developed by rational reactivity tuning. Tuning was achieved by selecting an electron-withdrawing para substituent in combination with variation of the number of fluorine substituents. Optimized probes chemoselectively arylated cysteine residues in proteins under aqueous conditions. Probes linked to azide, biotin, or a fluorophore were applicable to labeling of eGFP and albumin. Selective inhibition of cysteine proteases was also demonstrated with the probes. Additionally, probes were tuned for site-selective labeling of cysteine residues and for activity-based protein profiling in cell lysates.

Bioremediation of Crude Oil Contaminated Desert Soil: Effect of Biostimulation, Bioaugmentation and Bioavailability in Biopile Treatment Systems.

This work was aimed at evaluating the relative merits of bioaugmentation, biostimulation and surfactant-enhanced bioavailability of a desert soil contaminated by crude oil through biopile treatment. The results show that the desert soil required bioaugmentation and biostimulation for bioremediation of crude oil. The bioaugmented biopile system led to a total petroleum hydrocarbon (TPH) reduction of 77% over 156 days while the system with polyoxyethylene (20) sorbitan monooleate (Tween 80) gave a 56% decrease in TPH. The biostimulated system with indigenous micro-organisms gave 23% reduction in TPH. The control system gave 4% TPH reduction. The addition of Tween 80 led to a respiration rate that peaked in 48 days compared to 88 days for the bioaugmented system and respiration declined rapidly due to nitrogen depletion. The residual hydrocarbon in the biopile systems studied contained polyaromatics (PAH) in quantities that may be considered as hazardous. Nitrogen was found to be a limiting nutrient in desert soil bioremediation.